title: Neuroprotective, neuroplastic, and neurobehavioral effects of daily treatment with levetiracetam in experimental traumatic brain injury.
abstract: BACKGROUND
  Prophylactic treatment with antiepileptic drugs (AEDs) has been recommended to prevent early seizure onset in patients with traumatic brain injury (TBI). However, the potential neuroprotective and/or detrimental effects of prophylactic AED treatment on behavioral and cognitive function after TBI are not well studied.
  
  
  OBJECTIVE
  To investigate the effects of a novel AED, levitiracetam (LEV), on behavioral and cognitive function after experimental TBI in rats.
  
  
  METHODS
  Adult male rats were administered LEV (intraperitoneal 50 mg/kg) or vehicle (saline; SL) daily for 20 days beginning 1 day after controlled cortical impact (CCI; 2.8 mm; 4 m/s) or sham surgery. Beam performance (days 1-6), Y-maze (day 7), and Morris water maze (days 14-19) postinjury testing was assessed.
  
  
  RESULTS
  Daily LEV treatment improved motor function, increased novel arm exploration in the Y-maze, elicited greater hippocampal cell sparing, and decreased contusion volumes compared with CCI/SL rats. Daily LEV administration also reversed a TBI-induced decrease in regional glutamate transporter expression and neuroplastic marker proteins present 20 days post-CCI. Also, daily LEV treatment decreased regional IL-1β expression after TBI.
  
  
  CONCLUSIONS
  These results suggest that daily LEV treatment has beneficial effects on histological, molecular, and behavioral elements of neurological recovery after TBI, in part, via modulation of neuroinflammatory and excitatory pathways.
authors.affiliation: 1Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Huichao
authors.initials: H
authors.lastname: Zou
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Brayer
authors.forename: Maxwell
authors.initials: M
authors.lastname: Hurwitz
authors.forename: Christian
authors.initials: C
authors.lastname: Niyonkuru
authors.forename: Lorraine E
authors.initials: LE
authors.lastname: Fowler
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D000077287:Levetiracetam; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D027322:Amino Acid Transport System X-AG; D000927:Anticonvulsants; D018696:Neuroprotective Agents; D000077287:Levetiracetam; D010889:Piracetam
keywords: glutamate transporter; levitiracetam; neuroinflammation; neuroplasticity; neuroprotection; traumatic brain injury